반응 #88033

반응 방정식

K2CO3

4-(2-chloroethyl)morpholine hydrochloride

ethyl 5-amino-4-methoxythiophene-2-carboxylate

methanesulfonyl chloride

→

ethyl 4-methoxy-5-(N-(2-morpholinoethyl)-methylsulfonamido)thiophene-2-carboxylate

용매

pyridine

반응 조건

후처리

1. 1
   기타The solvent was removed under vacuum
2. 2
   세척the organic phase was washed with brine
3. 3
   건조dried over sodium sulfate
4. 4
   기타The solvent was removed under vacuum
5. 5
   workup.DISSOLUTIONthe residue was dissolved in dry DMF (10 ml)
6. 6
   온도the resulting mixture was heated to 80° C.
7. 7
   workup.STIRRINGstirred at this temperature for 3 hours
8. 8
   기타The solvent was removed under vacuum
9. 9
   workup.DISSOLUTIONthe residue was dissolved in EtOAc
10. 10
    세척washed with brine
11. 11
    건조The organic phase was dried over sodium sulfate
12. 12
    여과filtered
13. 13
    기타evaporated
14. 14
    여과The residue was purified by filtration on silica gel cartridge (DCM/EtOAc=8/2 to EtOAc)

실험 절차

To a solution of ethyl 5-amino-4-methoxythiophene-2-carboxylate (Int. 69) (261 mg, 1.297 mmol) (prepared as described in Step 5 hereabove reported) in pyridine (10 ml) cooled to 0° C., methanesulfonyl chloride (0.131 ml, 1.686 mmol) was added, and the reaction was allowed to warm to RT and stirred overnight. The solvent was removed under vacuum and the residue was portioned between EtOAc and 10% HCl; the organic phase was washed with brine and dried over sodium sulfate. The solvent was removed under vacuum and the residue was dissolved in dry DMF (10 ml); K2CO3 (448 mg, 3.24 mmol) and 4-(2-chloroethyl)morpholine hydrochloride (362 mg, 1.946 mmol) were added in one portion, and the resulting mixture was heated to 80° C. and stirred at this temperature for 3 hours. The solvent was removed under vacuum, and the residue was dissolved in EtOAc and washed with brine. The organic phase was dried over sodium sulfate, filtered evaporated. The residue was purified by filtration on silica gel cartridge (DCM/EtOAc=8/2 to EtOAc) to afford ethyl 4-methoxy-5-(N-(2-morpholinoethyl)-methylsulfonamido)thiophene-2-carboxylate (Int. 70) in a mixture with approximately 30% of corresponding methyl ester (375 mg, 0.955 mmol, MS/ESI+392.8 [MH]+). This intermediate was used as such in the following step considering it was a single product.

출처